Microbiological Evaluation of Two Mexican Artisanal Cheeses: Analysis of Foodborne Pathogenic Bacteria in Cotija Cheese and Bola de Ocosingo Cheese by qPCR.

Cotija and Bola de Ocosingo are artisanal ripened cheeses produced in Mexico. Both are made with raw bovine milk from free-grazing cows and with no starter cultures. Unlike culture-based techniques, molecular methods for pathogen detection in food allow a shorter turnaround time, higher detection specificity, and represent a lower microbiological risk for the analyst. In the present investigation, we analyzed 111 cheese samples (95 Cotija and 16 Bola de Ocosingo) by qPCR (TaqMan®) after an enrichment-culture step specific to each foodborne bacterium. The results showed that 100% of the samples were free of DNA from Listeria monocytogenes, Brucella spp., Escherichia coli enterotoxigenic (ETEC), and O157:H7; 9% amplified Salmonella spp. DNA; and 11.7%, Staphylococcus aureus DNA. However, the threshold cycle (Ct) values of the amplified targets ranged between 23 and 30, indicating DNA from non-viable microorganisms. Plate counts supported this assumption. In conclusion, 100% of the cheeses analyzed were safe to consume, and the enrichment step before DNA extraction proved essential to discern between viable and non-viable microorganisms. Hygienic milking, milk handling, cheese manufacturing, and ripening are crucial to achieve an adequate microbiological quality of cheeses made with raw milk.

Allergic contact dermatitis in adults with and without atopic dermatitis: Evaluation of the Spanish Contact Dermatitis Registry (REIDAC).

BACKGROUND: Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are inflammatory skin conditions whose association is not clearly defined. OBJECTIVES: To identify differences in ACD profile between patients with and without AD among those referred for patch testing. Additionally, to determine the prevalence of sensitisation to standard Spanish contact allergens in both groups. METHODS: We analysed two groups (AD and non-AD) within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy (REIDAC). Contact allergy, clinical relevance and epidemiological data were compared between them. RESULTS: A total of 5055 patients were included. Among them, 23% (1168) had a history or final diagnosis of AD. At least one positive reaction was seen in 468 (40%) of AD patients and 1864 (48%) of non-AD patients. In both groups, the most common positive reactions were to nickel sulphate, methylchloroisothiazolinone/methylisothiazolinone and cobalt chloride. Age-adjusted OR for sensitisation to nickel sulphate was 0.72 (95% CI: 0.61-0.86), indicating a decreased likelihood of sensitisation in AD patients compared to non-AD individuals. CONCLUSIONS: We did not find an increased presence of ACD in patients with AD referred for patch testing, exhibiting similar profiles to non-AD population, except for a negative relationship between AD and sensitisation to nickel sulphate.

Influence of extracellular ATP on mammalian sperm physiology.

In addition to its central role in cellular metabolism, adenosine 5'-triphosphate (ATP) is an important extracellular signalling molecule involved in various physiological processes. In reproduction, extracellular ATP participates in both autocrine and paracrine paths regulating gametogenesis, gamete maturation and fertilisation. This review focusses on how extracellular ATP modulates sperm physiology with emphasis on the mammalian acrosome reaction. The presence of extracellular ATP in the reproductive tract is primarily determined by the ion channels and transporters that influence its movement within the cells comprising the tract. The main targets of extracellular ATP in spermatozoa are its own transporters, particularly species-specific sperm purinergic receptors. We also discuss notable phenotypes from knock-out mouse models and human Mendelian inheritance related to ATP release mechanisms, along with immunological, proteomic, and functional observations regarding sperm purinergic receptors and their involvement in sperm signalling.

Beyond biomass production: Enhancing biodiversity while capturing carbon in short rotation coppice poplar plantations.

Biodiversity is essential for the functioning of ecosystems and the provision of services. In recent years, the role of plantations in mitigating climate change through carbon sequestration has been highlighted. In the Mediterranean area, high-density poplar plantations in short-rotation with resprouting management (SRC) have been established for biomass purposes on mostly irrigated agricultural land, coexisting with rainfed and irrigated agricultural crops. This study aims to assess the contribution of these plantations to this type of agroforest ecosystem in terms of biodiversity. For this purpose, both flora and fauna diversity were evaluated both within and outside of the plantation. Additionally, the accumulated carbon in the biomass, as well as in the accompanying vegetation within the plantation, was assessed. Different indices were used to evaluate both the intrinsic diversity of the forest plantation and the degree of substitution and complementarity between the different communities of the landscape. Our findings reveal distinct biodiversity patterns in the land-use scenarios sampled. Specifically, we observed significantly higher flora-species richness in SRC plantations than in the adjacent agricultural land, whereas fauna richness showed a similar but slightly higher level in the forested area. A moderate level of complementarity between land uses was found for insects and mammals (around 45 %), contrasting with high complementarity for birds (87 %) and flora (90 %). This suggests substantial turnover and replacement among these ecological environments. Our results indicate that a second rotation (4 year) plantation could accumulate a total of 61.6 Mg C ha-1, and even though adventitious flora represents <2 % of the total carbon accumulated, its importance in providing ecosystem services is considerable. Hence, these findings evidence the fact that SRC poplar plantations can enhance biodiversity in Mediterranean agroforest ecosystems and actively contribute to various provisioning ecosystem services, including carbon sequestration, reflecting a multi-objective approach that extends beyond biomass production.

Can the Dose of Belimumab be Reduced in Patients with Systemic Lupus Erythematosus?

OBJECTIVES: The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control of disease activity. METHODS: Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared. RESULTS: A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients.Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant [NS]). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62-8.75] vs 2.5 [0-5] at baseline). CONCLUSION: Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.

Alta frecuencia de trombo endoluminal en pacientes con ictus isquémico tras la infección por coronavirus 2019 / High frequency of endoluminal thrombus in patients with ischaemic stroke following SARS-CoV-2 infection

Introducción El ictus isquémico puede ser una complicación grave en los pacientes con infección por SARS-CoV-2. Estudiar y caracterizar los diferentes subtipos etiológicos, las características clínicas y el pronóstico funcional podrá resultar útil en la selección de pacientes para un manejo y tratamiento óptimos. Métodos La recogida de variables se hizo de forma retrospectiva en pacientes consecutivos con infección por SARS-CoV-2 que desarrollaron un episodio de isquemia cerebral focal (entre el 1 de marzo del 2020 y el 19 de abril del 2020). Se llevó a cabo en un hospital universitario de tercer nivel en la Comunidad de Madrid (España). Resultados Durante el período de estudio 1.594 pacientes fueron diagnosticados de infección por SARS-CoV-2. Identificamos a 22 pacientes con ictus isquémico (1,38%); de estos, no cumplieron los criterios de inclusión 6. Un total de 16 pacientes con isquemia cerebral focal constituyeron la serie del estudio (15 con ictus isquémico y uno con accidente isquémico transitorio). En la valoración basal en el National Institutes of Health Stroke Scale la mediana fue de 9 (rango intercuartil: 16), la edad media ± desviación estándar fue de 73 ± 12,8 años; 12 pacientes fueron varones (75%). El tiempo desde los síntomas de COVID-19 hasta el ictus fue de 13 días. Se encontró oclusión de gran vaso en 12 pacientes (75%). El dímero-D estuvo elevado en el 87,5% y la proteína C reactiva en el 81,2% de los casos. La etiología más frecuente del ictus isquémico fue la aterotrombosis (9 pacientes, 56,3%) con un subtipo predominante que fue el trombo endoluminal sobre placa de ateroma (5 pacientes, 31,2%), 4 de ellos en la arteria carótida interna y uno de ellos en el arco aórtico. La mortalidad en nuestra serie fue del 44% (7 de 16 pacientes). Conclusiones En los pacientes con ictus y COVID-19 la etiología más frecuente fue la aterotrombótica, con una elevada frecuencia de trombo endoluminal sobre placa de ateroma... (AU)

Background Ischaemic stroke may be a major complication of SARS-CoV-2 infection. Studying and characterising the different aetiological subtypes, clinical characteristics, and functional outcomes may be valuable in guiding patient selection for optimal management and treatment. Methods Data were collected retrospectively on consecutive patients with SARS-CoV-2 infection who developed acute focal brain ischaemia (between 1 March and 19 April 2020) at a tertiary university hospital in Madrid (Spain). Results During the study period, 1594 patients were diagnosed with COVID-19. We found 22 patients with ischaemic stroke (1.38%), 6 of whom did not meet the inclusion criteria. The remaining 16 patients were included in the study (15 cases of ischaemic stroke and one case of transient ischaemic attack). Median baseline National Institutes of Health Stroke Scale score was 9 (interquartile range: 16), and mean (standard deviation) age was 73 years (12.8). Twelve patients (75%) were men. Mean time from COVID-19 symptom onset to stroke onset was 13 days. Large vessel occlusion was identified in 12 patients (75%). We detected elevated levels of D-dimer in 87.5% of patients and C-reactive protein in 81.2%. The main aetiology was atherothrombotic stroke (9 patients, 56.3%), with the predominant subtype being endoluminal thrombus (5 patients, 31.2%), involving the internal carotid artery in 4 cases and the aortic arch in one. The mortality rate in our series was 44% (7 of 16 patients). Conclusions In patients with COVID-19, the most frequent stroke aetiology was atherothrombosis, with a high proportion of endoluminal thrombus (31.2% of patients). Our clinical and laboratory data support COVID-19–associated coagulopathy as a relevant pathophysiological mechanism for ischaemic stroke in these patients. (AU)

Alta frecuencia de trombo endoluminal en pacientes con ictus isquémico tras la infección por coronavirus 2019 / High frequency of endoluminal thrombus in patients with ischaemic stroke following SARS-CoV-2 infection

Introducción El ictus isquémico puede ser una complicación grave en los pacientes con infección por SARS-CoV-2. Estudiar y caracterizar los diferentes subtipos etiológicos, las características clínicas y el pronóstico funcional podrá resultar útil en la selección de pacientes para un manejo y tratamiento óptimos. Métodos La recogida de variables se hizo de forma retrospectiva en pacientes consecutivos con infección por SARS-CoV-2 que desarrollaron un episodio de isquemia cerebral focal (entre el 1 de marzo del 2020 y el 19 de abril del 2020). Se llevó a cabo en un hospital universitario de tercer nivel en la Comunidad de Madrid (España). Resultados Durante el período de estudio 1.594 pacientes fueron diagnosticados de infección por SARS-CoV-2. Identificamos a 22 pacientes con ictus isquémico (1,38%); de estos, no cumplieron los criterios de inclusión 6. Un total de 16 pacientes con isquemia cerebral focal constituyeron la serie del estudio (15 con ictus isquémico y uno con accidente isquémico transitorio). En la valoración basal en el National Institutes of Health Stroke Scale la mediana fue de 9 (rango intercuartil: 16), la edad media ± desviación estándar fue de 73 ± 12,8 años; 12 pacientes fueron varones (75%). El tiempo desde los síntomas de COVID-19 hasta el ictus fue de 13 días. Se encontró oclusión de gran vaso en 12 pacientes (75%). El dímero-D estuvo elevado en el 87,5% y la proteína C reactiva en el 81,2% de los casos. La etiología más frecuente del ictus isquémico fue la aterotrombosis (9 pacientes, 56,3%) con un subtipo predominante que fue el trombo endoluminal sobre placa de ateroma (5 pacientes, 31,2%), 4 de ellos en la arteria carótida interna y uno de ellos en el arco aórtico. La mortalidad en nuestra serie fue del 44% (7 de 16 pacientes). Conclusiones En los pacientes con ictus y COVID-19 la etiología más frecuente fue la aterotrombótica, con una elevada frecuencia de trombo endoluminal sobre placa de ateroma... (AU)

Background Ischaemic stroke may be a major complication of SARS-CoV-2 infection. Studying and characterising the different aetiological subtypes, clinical characteristics, and functional outcomes may be valuable in guiding patient selection for optimal management and treatment. Methods Data were collected retrospectively on consecutive patients with SARS-CoV-2 infection who developed acute focal brain ischaemia (between 1 March and 19 April 2020) at a tertiary university hospital in Madrid (Spain). Results During the study period, 1594 patients were diagnosed with COVID-19. We found 22 patients with ischaemic stroke (1.38%), 6 of whom did not meet the inclusion criteria. The remaining 16 patients were included in the study (15 cases of ischaemic stroke and one case of transient ischaemic attack). Median baseline National Institutes of Health Stroke Scale score was 9 (interquartile range: 16), and mean (standard deviation) age was 73 years (12.8). Twelve patients (75%) were men. Mean time from COVID-19 symptom onset to stroke onset was 13 days. Large vessel occlusion was identified in 12 patients (75%). We detected elevated levels of D-dimer in 87.5% of patients and C-reactive protein in 81.2%. The main aetiology was atherothrombotic stroke (9 patients, 56.3%), with the predominant subtype being endoluminal thrombus (5 patients, 31.2%), involving the internal carotid artery in 4 cases and the aortic arch in one. The mortality rate in our series was 44% (7 of 16 patients). Conclusions In patients with COVID-19, the most frequent stroke aetiology was atherothrombosis, with a high proportion of endoluminal thrombus (31.2% of patients). Our clinical and laboratory data support COVID-19–associated coagulopathy as a relevant pathophysiological mechanism for ischaemic stroke in these patients. (AU)

Four-year Epidemiological Surveillance of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy: Current Situation and Trends. / Vigilancia epidemiológica en los últimos 4 años del Registro Español de Investigación en Dermatitis de Contacto y Alergia Cutánea: situación actual y tendencias.

BACKGROUND: The epidemiological surveillance of contact dermatitis is one of the objectives of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. Knowing whether the prevalence of positive tests to the different allergens changes over time is important for this monitoring process. OBJECTIVES: To describe the various temporary trends in allergen positivity in the GEIDAC standard series from 2018 through December 31, 2022. METHODS: This was a multicenter, observational trial of consecutive patients analyzed via patch tests as part of the study of possible allergic contact dermatitises collected prospectively within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. The data was analyzed using 2 statistical tests: one homogeneity test (to describe the changes seen over time) and one trend test (to see whether the changes described followed a linear trend). RESULTS: A total of 11327 patients were included in the study. Overall, the allergens associated with a highest sensitization were nickel sulfate, methylisothiazolinone, cobalt chloride, methylchloroisothiazolinone/methylisothiazolinone, and fragrance mix i. A statistically significant decrease was found in the percentage of methylisothiazolinone positive tests across the study years with an orderly trend. CONCLUSIONS: Although various changes were seen in the sensitizations trends to several allergens of the standard testing, it became obvious that a high sensitization to nickel, methylchloroisothiazolinone/methylisothiazolinone and fragrances mix i remained. Only a significant downward trend was seen for methylisothiazolinone.

High frequency of endoluminal thrombus in patients with ischaemic stroke following AARS-CoV-2 infection.

BACKGROUND: Ischaemic stroke may be a major complication of SARS-CoV-2 infection. Studying and characterising the different aetiological subtypes, clinical characteristics, and functional outcomes may be valuable in guiding patient selection for optimal management and treatment. METHODS: Data were collected retrospectively on consecutive patients with COVID-19 who developed acute focal brain ischaemia (between 1 March and 19 April 2020) at a tertiary university hospital in Madrid (Spain). RESULTS: During the study period, 1594 patients were diagnosed with COVID-19. We found 22 patients with ischaemic stroke (1.38%), 6 of whom did not meet the inclusion criteria. The remaining 16 patients were included in the study (15 cases of ischaemic stroke and one case of transient ischaemic attack). Median baseline National Institutes of Health Stroke Scale score was 9 (interquartile range: 16), and mean (standard deviation) age was 73 years (12.8). Twelve patients (75%) were men. Mean time from COVID-19 symptom onset to stroke onset was 13 days. Large vessel occlusion was identified in 12 patients (75%). We detected elevated levels of D-dimer in 87.5% of patients and C-reactive protein in 81.2%. The main aetiology was atherothrombotic stroke (9 patients, 56.3%), with the predominant subtype being endoluminal thrombus (5 patients, 31.2%), involving the internal carotid artery in 4 cases and the aortic arch in one. The mortality rate in our series was 44% (7 of 16 patients). CONCLUSIONS: In patients with COVID-19, the most frequent stroke aetiology was atherothrombosis, with a high proportion of endoluminal thrombus (31.2% of patients). Our clinical and laboratory data support COVID-19-associated coagulopathy as a relevant pathophysiological mechanism for ischaemic stroke in these patients.

Clinical presentation, management, and survival in dogs with persistent atrial standstill in the United Kingdom.

OBJECTIVES: To investigate the clinical and echocardiographic presentation of dogs with persistent atrial standstill (PAS), identify variables measured at first presentation that could predict their survival, and document the progression of the disease after pacing. MATERIALS AND METHODS: Retrospective study of medical records of dogs diagnosed with PAS at three referral hospitals of the United Kingdom over seven years. RESULTS: Twenty-six dogs were diagnosed with PAS during the study period. Median age of the population was three years (range: seven months-12.5 years). The most common clinical sign was syncope (14/26). Twenty-four dogs received artificial pacemakers (PM). Major complications after PM implantation were observed in four dogs (four/24). Serial echocardiographic examinations showed that cardiac dimensions of PAS dogs with left atrial or left ventricular dilation at first presentation did not return to reference range after pacing. Further dilation of the cardiac chambers, recurrence of congestive heart failure (CHF), or development of new episodes of CHF were documented in seven, four, and 10 PAS dogs, respectively, despite pacing. Median survival time for cardiac-related deaths after PM implantation was 1512 days (18-3207). Neither CHF nor echocardiographic variables at presentation predicted survival after PM implantation in PAS dogs. CONCLUSIONS: Persistent atrial standstill (PAS) is an uncommon bradyarrhythmia, occurring in young adult dogs. Affected dogs were often presented with syncope. Whilst syncope resolved, cardiac remodeling persisted after PM implantation. Long-term survival was favorable after PM implantation and was not predicted by congestive status or cardiac chamber size at first presentation.

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse / Avaliação genotóxica e citotóxica da venlafaxina em ensaio agudo e subcrônico em camundongos

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

Intra-annual density fluctuations in tree rings are proxies of air temperature across Europe.

Intra-Annual Density Fluctuations (IADFs) are an important wood functional trait that determine trees' ability to adapt to climatic changes. Here, we use a large tree-ring database of 11 species from 89 sites across eight European countries, covering a climatic gradient from the Mediterranean to northern Europe, to analyze how climate variations drive IADF formation. We found that IADF occurrence increases nonlinearly with ring width in both gymnosperms and angiosperms and decreases with altitude and age. Recently recorded higher mean annual temperatures facilitate the formation of IADFs in almost all the studied species. Precipitation plays a significant role in inducing IADFs in species that exhibit drought tolerance capability, and a growth pattern known as bimodal growth. Our findings suggest that species with bimodal growth patterns growing in western and southern Europe will form IADFs more frequently, as an adaptation to increasing temperatures and droughts.

Utilidad del injerto de membrana amniótica en el manejo de la exposición del implante XEN® / Usefulness of the amniotic membrane graft in the management of the exposure of the XEN® implant

Se presenta el caso de una mujer de 79 años con glaucoma severo y falta de adherencia al tratamiento, que es sometida a cirugía de catarata e implante XEN® en su ojo izquierdo. Dos semanas después de la intervención se objetiva una erosión conjuntival con exposición del extremo distal del implante, por lo que se realiza una reparación quirúrgica mediante la combinación de una sutura aposicional del tubo, adaptando su trayectoria a la curvatura escleral, y el recubrimiento con injerto de membrana amniótica. Tras 6 meses de seguimiento, presenta una presión intraocular controlada, sin necesidad de tratamiento adicional, y sin mostrar progresión de su enfermedad (AU)

We report a case of a 79-year-old woman with severe glaucoma and absence of therapeutic adherence, who underwent cataract surgery and XEN® implant in her left eye. Two weeks after the intervention, conjunctival erosion was observed with exposure of the distal end of the implant, so a surgical repair was performed by combining an appositional suture of the tube, adapting its trajectory to the scleral curvature, and an amniotic membrane graft. After 6 months of follow-up, the intraocular pressure was controlled, without additional treatment needed, and no disease progression (AU)

Detecting stress caused by nitrogen deficit using deep learning techniques applied on plant electrophysiological data.

Plant electrophysiology carries a strong potential for assessing the health of a plant. Current literature for the classification of plant electrophysiology generally comprises classical methods based on signal features that portray a simplification of the raw data and introduce a high computational cost. The Deep Learning (DL) techniques automatically learn the classification targets from the input data, overcoming the need for precalculated features. However, they are scarcely explored for identifying plant stress on electrophysiological recordings. This study applies DL techniques to the raw electrophysiological data from 16 tomato plants growing in typical production conditions to detect the presence of stress caused by a nitrogen deficiency. The proposed approach predicts the stressed state with an accuracy of around 88%, which could be increased to over 96% using a combination of the obtained prediction confidences. It outperforms the current state-of-the-art with over 8% higher accuracy and a potential for a direct application in production conditions. Moreover, the proposed approach demonstrates the ability to detect the presence of stress at its early stage. Overall, the presented findings suggest new means to automatize and improve agricultural practices with the aim of sustainability.

ATP increases head volume in capacitated human sperm via a purinergic channel.

Scanning ion-conductance microscopy allowed us to document an external Ca2+ dependent ATP driven volume increase (ATPVI) in capacitated human sperm heads. We examined the involvement of purinergic receptors (PRs) P2X2R and P2X4R in ATPVI using their co-agonists progesterone and Ivermectin (Iver), and Cu2+, which co-activates P2X2Rs and inhibits P2X4Rs. Iver enhanced ATPVI and Cu2+ and 5BDBD inhibited it, indicating P2X4Rs contributed to this response. Moreover, Cu2+ and 5BDBD inhibited the ATP-induced acrosome reaction (AR) which was enhanced by Iver. ATP increased the concentration of intracellular Ca2+ ([Ca2+]i) in >45% of individual sperm, most of which underwent AR monitored using FM4-64. Our findings suggest that human sperm P2X4R activation by ATP increases [Ca2+]i mainly due to Ca2+ influx which leads to a sperm head volume increase, likely involving acrosomal swelling, and resulting in AR.

Alemtuzumab treatment in real clinical practice: Experience in a multicenter cohort.

BACKGROUND: Alemtuzumab is a highly effective treatment for relapsing remitting multiple sclerosis (RRMS), but in recent years safety-related concerns had emerged due to description of novel serious side effects not registered in CARE-MS I and CARE-MS II phase 3 studies, nor in TOPAZ extension study. Data about alemtuzumab use in real clinical practice are limited and based mainly on retrospective studies with small sample sizes. Therefore, more information about effectiveness and safety of alemtuzumab in this context is needed. METHODS: A multicenter observational prospective study to investigate effectivity and safety of alemtuzumab in a real-world setting was performed. Primary endpoints were the change in annualized relapse rate (ARR), and in disability measured by EDSS score. Secondary endpoints were the cumulative probability of confirmed 6-month disability improvement and worsening. Disability worsening and disability improvement were considered when the EDSS score was increased or decreased, respectively, in 1 point if baseline EDSS score was <5.0, or in 0.5 point if baseline EDSS score was ≥5.5, confirmed over 6 months. Other secondary endpoint was the proportion of patients who achieved NEDA-3 status (absence of clinical relapses, disability EDSS progression, and MRI disease activity as depicted by new/enlarging T2 lesions or Gadolinium enhancing T1 lesions). Adverse events also were recorded. RESULTS: A total of 195 RRMS patients (70% female) who started alemtuzumab treatment were included. Mean of follow-up was 2.38 years. Alemtuzumab significantly reduced the annualized relapse rate from baseline with risk reductions of 86%, 83.5%, and 84%, at 12, 24, and 36 months of follow-up respectively (Friedman test, p-value < 0.05 for all comparisons). Alemtuzumab also significantly reduced EDSS score over one and two years after starting alemtuzumab treatment (Friedman test, p-value<0.001 for both comparisons). A high proportion of patients presented confirmed 6-month stability or disability improvement (92%, 82%, and 79%, over 1, 2 and 3 years of follow-up respectively). The proportion of patients who retained NEDA-3 status at 12, 24 and 36 months were 61%, 49%, and 42%, respectively. Baseline characteristics associated with a lower probability of achieving NEDA-3 were younger age, sex female, high ARR, elevated number of previous treatments, and switch from a second line therapy. Infusion related reactions were the most frequent adverse event observed. The most common infections were urinary tract infections (50%), and upper respiratory tract infections (19%) over the 3 years of follow- up. Secondary thyroid autoimmunity was developed in 18.5% of patients. CONCLUSION: Alemtuzumab has demonstrated in real clinical practice high effectiveness in controlling multiple sclerosis activity, and no unexpected adverse events were observed.